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BACKGROUND & AIMS: Polygenic risk scores (PRSs) could help to define personalized colorectal cancer (CRC) screening strategies. The aim of this study was to evaluate whether a PRS, along with adenoma characteristics, could help to define more personalized and risk-adapted surveillance intervals. METHODS: In a population-based, case-control study from Germany, detailed information on previous colonoscopies and a PRS based on 140 CRC-related, single-nucleotide polymorphisms was obtained from 4696 CRC cases and 3709 controls. Participants were classified as having low, medium, or high genetic risk according to tertiles of PRSs among controls. We calculated the absolute risk of CRC based on the PRS and colonoscopy history and findings. RESULTS: We observed major variations of CRC risk according to the PRS, including among individuals with detection and removal of adenomas at colonoscopy. For instance, the estimated 10-year absolute risk of CRC for 50-year-old men and women with no polyps, for whom repeat screening colonoscopy is recommended after 10 years only, was 0.2%. Equivalent absolute risks were estimated for people with low-risk adenomas and low PRS. However, the same levels of absolute risk were reached within 3 to 5 years by those with low-risk adenomas and high PRS and with high-risk adenomas irrespective of the PRS. CONCLUSIONS: Consideration of genetic predisposition to CRC risk, as determined by a PRS, could help to define personalized, risk-adapted surveillance intervals after detection and removal of adenomas at screening colonoscopy. However, whether the risk variation is strong enough to direct clinical risk stratification needs to be explored further.
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Pólipos Adenomatosos , Neoplasias Colorrectales , Detección Precoz del Cáncer , Herencia Multifactorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Factores de Riesgo , Pólipos Adenomatosos/patología , Pólipos Adenomatosos/cirugíaRESUMEN
BACKGROUND: Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent. OBJECTIVE: To evaluate disability-free survival (DFS) in older individuals by glycaemic status. METHODS: This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70 years, who had no prior cardiovascular events, dementia and physical disability. Participants with sufficient information to ascertain their baseline diabetes status were categorised as having normoglycaemia (fasting plasma glucose [FPG] < 5.6 mmol/l, 64%), prediabetes (FPG 5.6 to <7.0 mmol/l, 26%) and diabetes (self-report or FPG ≥ 7.0 mmol/l or use of glucose-lowering agents, 11%). The primary outcome was loss of disability-free survival (DFS), a composite of all-cause mortality, persistent physical disability or dementia. Other outcomes included the three individual components of the DFS loss, as well as cognitive impairment-no dementia (CIND), major adverse cardiovascular events (MACE) and any cardiovascular event. Cox models were used for outcome analyses, with covariate adjustment using inverse-probability weighting. RESULTS: We included 18,816 participants (median follow-up: 6.9 years). Compared to normoglycaemia, participants with diabetes had greater risks of DFS loss (weighted HR: 1.39, 95% CI 1.21-1.60), all-cause mortality (1.45, 1.23-1.72), persistent physical disability (1.73, 1.35-2.22), CIND (1.22, 1.08-1.38), MACE (1.30, 1.04-1.63) and cardiovascular events (1.25, 1.02-1.54) but not dementia (1.13, 0.87-1.47). The prediabetes group did not have an excess risk for DFS loss (1.02, 0.93-1.12) or other outcomes. CONCLUSIONS: Among older people, diabetes was associated with reduced DFS, and higher risk of CIND and cardiovascular outcomes, whereas prediabetes was not. The impact of preventing or treating diabetes in this age group deserves closer attention.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Estado Prediabético , Anciano , Humanos , Aspirina , Diabetes Mellitus/diagnóstico , Estado Prediabético/diagnóstico , Estado Prediabético/tratamiento farmacológico , Pronóstico , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & controlRESUMEN
BACKGROUND: Unhealthy lifestyle behaviours such as smoking, high alcohol consumption, poor diet or low physical activity are associated with morbidity and mortality. Public health guidelines provide recommendations for adherence to these four factors, however, their relationship to the health of older people is less certain. METHODS: The study involved 11,340 Australian participants (median age 7.39 [Interquartile Range (IQR) 71.7, 77.3]) from the ASPirin in Reducing Events in the Elderly study, followed for a median of 6.8 years (IQR: 5.7, 7.9). We investigated whether a point-based lifestyle score based on adherence to guidelines for a healthy diet, physical activity, non-smoking and moderate alcohol consumption was associated with subsequent all-cause and cause-specific mortality. RESULTS: In multivariable adjusted models, compared to those in the unfavourable lifestyle group, individuals in the moderate lifestyle group (Hazard Ratio (HR) 0.73 [95% CI 0.61, 0.88]) and favourable lifestyle group (HR 0.68 [95% CI 0.56, 0.83]) had lower risk of all-cause mortality. A similar pattern was observed for cardiovascular related mortality and non-cancer/non-cardiovascular related mortality. There was no association of lifestyle with cancer-related mortality. CONCLUSIONS: In a large cohort of initially healthy older people, reported adherence to a healthy lifestyle is associated with reduced risk of all-cause and cause-specific mortality. Adherence to all four lifestyle factors resulted in the strongest protection.
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Estilo de Vida Saludable , Mortalidad , Anciano , Humanos , Australia/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Conductas Relacionadas con la Salud , Estilo de Vida , Estudios Prospectivos , Factores de Riesgo , Dieta Saludable/mortalidad , Dieta Saludable/estadística & datos numéricos , Ejercicio Físico/estadística & datos numéricos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/mortalidad , Fumar/epidemiología , Fumar/mortalidad , Neoplasias/epidemiología , Neoplasias/mortalidadRESUMEN
BACKGROUND: Little is known about how changes in a constellation of lifestyle factors affect health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. Our study aimed to investigate the association between changes in healthy lifestyle and HRQoL over time in survivors of stage I-IV CRC. METHODS: We included 2,283 long-term (≥5 years postdiagnosis) survivors. A healthy lifestyle score (HLS) comprising smoking, alcohol consumption, diet, physical activity, and body fatness was derived at diagnosis and 5-year follow-up (5YFU) and categorized as low, moderate, or high. We assessed HRQoL with the EORTC Quality of Life Questionnaire-Core 30 at 5YFU and 10-year follow-up. We used multivariable linear regression and linear mixed models to explore associations between changes in HLS and HRQoL over follow-up. RESULTS: A low baseline HLS was associated with poorer functioning and global health/QoL and a higher symptom burden at 5YFU compared with a high baseline HLS. An improved HLS from baseline to 5YFU was associated with better functioning, higher global health/QoL, and fewer symptoms at 5YFU than a maintained-high HLS. In longitudinal analyses, improved HLS was associated with better functioning at follow-up. Survivors with a maintained-high or an improved HLS reported generally less fatigue, pain, and dyspnea at follow-ups compared with survivors with a maintained-low or decreased HLS. CONCLUSIONS: Change toward a healthier lifestyle since diagnosis was associated with better HRQoL in long-term CRC survivors. Our results support the importance of maintaining and/or promoting a healthier lifestyle among CRC survivors postdiagnosis.
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Neoplasias Colorrectales , Calidad de Vida , Humanos , Estilo de Vida Saludable , Estilo de Vida , Sobrevivientes , Neoplasias Colorrectales/complicaciones , Encuestas y CuestionariosRESUMEN
PURPOSE OF REVIEW: Cardiovascular disease is long-term complication of both cancer and anti-cancer treatment and can have significant ramifications for health-related quality of life and mortality. This narrative review explores the current evidence linking cardiovascular disease and cancer, as well as exploring strategies for the prevention and management of cardiovascular disease, and outlines future opportunities in the field of cardio-oncology. RECENT FINDINGS: Cancer confers risk for various cardiovascular diseases including heart failure, cardiomyopathy, arrhythmia, coronary heart disease, stroke, venous thromboembolism, and valvular heart disease. Cancer treatment, in particular agents such as platinum-based chemotherapy, anthracyclines, hormonal treatments, and thoracic radiotherapy, further increases risk. While cardiovascular disease can be identified early and effectively managed in cancer survivors, cardiovascular screening and management does not typically feature in routine long-term cancer care of adult cancer survivors. Cancer and cancer treatment can accelerate the development of cardiovascular disease. Further research into screening and management strategies for cardiovascular disease, along with evidence-based guidelines, is required to ensure adult cancer survivors receive appropriate long-term care.
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Antineoplásicos , Supervivientes de Cáncer , Enfermedades Cardiovasculares , Neoplasias , Adulto , Humanos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/prevención & control , Calidad de Vida , Antineoplásicos/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Antraciclinas/uso terapéuticoRESUMEN
BACKGROUND: Existing studies have illustrated how the onset of physical disability or dementia negatively impacts economic wellbeing and increases out of pocket costs. However, little is known about this relationship in older individuals. Consequently, this study aimed to identify how the onset of physical disability or dementia in older adults affects economic wellbeing and out of pocket costs, and to explore the impact of gender in the context of Australia. METHODS: The data was collected from a large, randomized clinical study, ASPirin in Reducing Events in the Elderly (ASPREE). Two generalized linear models (with and without interaction effects) of total out of pocket costs for those who did and did not develop physical disability or dementia were generated, with adjustment for sociodemographic characteristics at baseline. RESULTS: We included 8,568 older Australian individuals with a mean age of 74.8 years and 53.2% being females. After adjustment for the baseline sociodemographic characteristics, the onset of physical disability did statistically significantly raise out of pocket costs (cost ratio = 1.25) and costs among females were 13.1% higher than males. CONCLUSIONS: This study highlights that classifying different types of health conditions to identify the drivers of out of pocket costs and to explore the gender differences in a long-term follow-up is of importance to examine the financial impact on the older population. These negative financial impacts and gender disparities of physical disability and dementia must be considered by policymakers.
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Demencia , Personas con Discapacidad , Anciano , Aspirina , Australia/epidemiología , Demencia/epidemiología , Femenino , Gastos en Salud , Humanos , MasculinoRESUMEN
OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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Colon , Neoplasias del Colon/genética , Heterogeneidad Genética , Neoplasias del Recto/genética , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Ciego , Colon Ascendente , Colon Descendente , Colon Sigmoide , Colon Transverso , Neoplasias del Colon/diagnóstico , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Neoplasias del Recto/diagnóstico , Factores de Riesgo , Población Blanca/genética , Adulto JovenRESUMEN
BACKGROUND & AIMS: Estimates of absolute risk of colorectal cancer (CRC) are needed to facilitate communication and better inform the public about the potentials and limits of cancer prevention. METHODS: Using data from a large population-based case-control study in Germany (Darmkrebs: Chancen der Verhütung durch Screening [DACHS] study, which began in 2003) and population registry data, we calculated 30-year absolute risk estimates for development of CRC based on a healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness), a polygenic risk score (based on 90 single-nucleotide polymorphisms), and colonoscopy history. RESULTS: We analyzed data from 4220 patients with CRC and 3338 individuals without CRC. Adherence to a healthy lifestyle and colonoscopy in the preceding 10 years were associated with a reduced relative risk of CRC in men and women. We observed a higher CRC risk in participants with high or intermediate genetic risk scores. For 50-year-old men and women without a colonoscopy, the absolute risk of CRC varied according to the polygenic risk score and the healthy lifestyle score (men, 3.5%-13.4%; women, 2.5%-10.6%). For 50-year-old men and women with a colonoscopy, the absolute risk of developing CRC was much lower but still varied according to the polygenic risk score and the healthy lifestyle score (men, 1.2%-4.8%; women, 0.9%-4.2%). Among all risk factor profiles, the 30-year absolute risk estimates consistently decreased with adherence to a healthy lifestyle. CONCLUSIONS: In a population-based study, we found that a colonoscopy can drastically reduce the absolute risk of CRC and that the genetically predetermined risk of CRC can be further reduced by adherence to a healthy lifestyle. Our results show the magnitude of CRC prevention possible through colonoscopy and lifestyle at a predefined genetic risk. This observational study has been registered in the German Clinical Trials Register (DRKS00011793), which is a primary registry in the World Health Organization Registry Network.
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Biomarcadores de Tumor/genética , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/epidemiología , Estilo de Vida Saludable , Tamizaje Masivo/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Femenino , Predisposición Genética a la Enfermedad , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de RiesgoRESUMEN
BACKGROUND: In the era of personalized medicine, cancer care is subject to major changes and innovations. It is unclear, however, to what extent implementation of such innovations and their impact on patient outcomes differ by health insurance type. This study compared provision of treatment and survival outcomes among patients with colorectal cancer (CRC) who had statutory health insurance (SHI) versus private health insurance (PHI) in Germany. METHODS: We analyzed patterns of CRC treatment (surgery, chemotherapy/radiotherapy, and targeted therapy) and survival in a large cohort of patients who were diagnosed with CRC in 2003 through 2014 and were observed for an average of 6 years. Associations of type of health insurance with treatment administration and with overall, CRC-specific, and recurrence-free survival were investigated using multivariable logistic and Cox proportional hazards models, respectively. RESULTS: Of 3,977 patients with CRC, 427 (11%) had PHI. Although type of health insurance was not associated with treatment administration in patients with stage I-III disease, those with stage IV disease with PHI more often received targeted therapy (65% vs 40%; odds ratio, 2.43; 95% CI, 1.20-4.91), with differences decreasing over time because of catch-up of uptake rates in patients with SHI. Median overall survival was longer in patients with PHI than in those with SHI (137.0 vs 114.9 months; P=.010), but survival advantages were explained to a large extent by differences in sociodemographic factors. In patients with stage IV disease, survival advantages of PHI were nonsignificant and were restricted to the early years after diagnosis. CONCLUSIONS: We observed major differences in uptake of targeted therapy between patients with PHI and those with SHI but no differences in patient survival after adjusting for relevant sociodemographic, clinical, and tumor characteristics. Further studies are needed on factors associated with the uptake of therapeutic innovations and their impact on patient survival by health insurance type.
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Neoplasias Colorrectales , Seguro de Salud/clasificación , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/terapia , Alemania , Humanos , Tasa de SupervivenciaRESUMEN
Human milk fatty acid composition varies during lactation and is influenced by maternal diet, maternal lifestyle-related factors and genetic background. This is one of the first studies to investigate a period effect, that is, the impact of lifestyle-related changes on human milk fatty acid composition, in two different cohorts. Lactating women were recruited from the general population a decade apart in Ulm, Germany, using similar methodology. Human milk samples collected 6 weeks postpartum were analysed (Ulm Birth Cohort Study (UBCS (2000)), n 567; Ulm SPATZ Health Study (SPATZ (2012)), n 458). Centred log ratio transformation was applied to fatty acid data. Principal component analysis was used to determine study-dependent fatty acid profiles. A general linear model was used to determine the study (or period) effect on fatty acid profiles adjusting for duration of gestation, age, education, delivery mode, smoking and pre-pregnancy BMI. Two principal components were retained (PC1 and PC2). PC1 was associated with UBCS, while PC2 was associated with SPATZ. PC1 comprised high SFA, and low MUFA, n-6 and n-3 long-chain PUFA (LCPUFA). The inverse was true for PC2. Although human milk remains a source of essential fatty acids, infants could be at risk of inadequate n-3 and n-6 LCPUFA intake through human milk. The differences in the human milk fatty acid profiles also reflect changes in maternal dietary habits in the more recent cohort, which may comprise lower intakes of dietary trans-fatty acids and SFA and higher intakes of vegetable oils.
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Ácidos Grasos/análisis , Estilo de Vida , Leche Humana , Cohorte de Nacimiento , Estudios de Cohortes , Dieta , Ácidos Grasos Esenciales/análisis , Femenino , Alemania , Humanos , Lactante , Lactancia , Leche Humana/química , EmbarazoRESUMEN
Postmenopausal hormone replacement therapy (HRT) was found to be associated with lower risk of colorectal cancer (CRC). However, little is known regarding associations with molecular subtypes of CRC. The current study includes female participants of a large German population-based case-control study (922 CRC cases and 1,183 controls). Tumor tissue samples were analyzed for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), BRAF and KRAS mutation status. Multivariable logistic regression models were used to assess the association of HRT use with molecular subtypes and pathways. Postmenopausal HRT use was overall associated with reduced risk of CRC (adjusted odds ratio (aOR) 0.62, 95% confidence interval (CI) 0.50-0.76) and no major differences were observed for molecular subtypes or for tumor marker combinations representing molecular pathways. When stratified by median age (≤/>71 years) potentially stronger risk reductions were observed in the older group for subtypes showing MSI (OR = 0.36, 95% CI 0.17-0.76), BRAF mutation (OR = 0.40, 95% CI 0.30-0.83) and CIMP-high (OR = 0.40, 95% CI 0.21-0.73) and for CRC suggestive of the sessile serrated pathway (OR = 0.45, 95% CI 0.20-1.01). In conclusion, postmenopausal use of HRT was similarly associated with risk reduction of major molecular tumor subtypes and pathways of CRC. Potentially stronger risk reductions with CRC subtypes diagnosed at higher ages require confirmation and clarification from other studies. The current study extends the limited understanding of the mechanisms of HRT in CRC prevention.
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Neoplasias Colorrectales/terapia , Terapia de Reemplazo de Estrógeno/métodos , Posmenopausia , Medición de Riesgo/estadística & datos numéricos , Anciano , Estudios de Casos y Controles , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Islas de CpG/genética , Metilación de ADN , Femenino , Alemania/epidemiología , Humanos , Modelos Logísticos , Inestabilidad de Microsatélites , Persona de Mediana Edad , Análisis Multivariante , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
BACKGROUND: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear. METHODS: This population-based case-control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways. RESULTS: Current smoking showed higher ORs for MSI-high (OR = 2.79, 95% CI: 1.86-4.18) compared to MSS (OR = 1.41, 1.14-1.75, p-heterogeneity (p-het) = 0.001), BRAF-mutated (mut) (OR = 2.40, 1.41-4.07) compared to BRAF-wild type (wt) (OR = 1.52, 1.24-1.88, p-het = 0.074), KRAS-wt (OR = 1.70, 1.36-2.13) compared to KRAS-mut (OR = 1.26, 0.95-1.68, p-het = 0.039) and CIMP-high (OR = 2.01, 1.40-2.88) compared to CIMP-low/negative CRC (OR = 1.50, 1.22-1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high + BRAF-mut; OR = 2.39, 1.27-4.52) than with traditional pathway CRC (MSS + CIMP-low/negative + BRAF-wt; OR = 1.50, 1.16-1.94) and no association was observed with alternate pathway CRC (MSS + CIMP-low/negative + KRAS-wt; OR = 1.08, 0.77-1.43). No heterogeneity was observed in alcohol consumption association by molecular subtypes. CONCLUSIONS: In this large case-control study, smoking was more strongly associated with MSI-high and KRAS-wt CRC and with cases showing features of the sessile serrated pathway. Association patterns were less clear for alcohol consumption.
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Consumo de Bebidas Alcohólicas/efectos adversos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Fumar/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proto-Oncogenes Mas , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Polygenic risk scores (PRSs) could help to define starting ages for colorectal cancer (CRC) screening. However, the role of PRS in determining the length of screening interval after negative findings from colonoscopies is unclear. We aimed to evaluate CRC risk according to PRS and time since last negative colonoscopy. METHODS: We collected data from 3827 cases and 2641 CRC-free controls in a population-based case-control study in Germany. We constructed a polygenic risk scoring system, based on 90 single-nucleotide polymorphisms, associated with risk of CRC in people of European descent. Participants were classified as having low, medium, or high genetic risk according to tertiles of PRSs among controls. Multiple logistic regression models were used to assess CRC risk according to PRS and time since last negative colonoscopy. RESULTS: Compared to individuals without colonoscopy in the low PRS category, a 42%-85% lower risk of CRC was observed for individuals who had a negative finding from colonoscopy within 10 years. Beyond 10 years after a negative finding from colonoscopy, significantly lower risk only persisted for the low and medium PRS groups, but not for the high PRS group. Adjusted odds ratios were 0.44 (95% CI, 0.29-0.68), 0.51 (95% CI, 0.34-0.77), and 0.85 (95% CI, 0.58-1.23) in the low, medium, and high PRS group, respectively. Within any time interval, risks were lower for distal than for proximal CRCs. CONCLUSIONS: Based on findings from a population-based case-control study, the recommended 10-year screening interval for colonoscopy may not need to be shortened among people with high PRSs, but could potentially be prolonged for people with low and medium PRSs. Studies are needed to address personalized time intervals for repeat colonoscopies in average-risk screening cohorts.
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Colonoscopía , Neoplasias Colorrectales , Estudios de Casos y Controles , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Detección Precoz del Cáncer , Humanos , Tamizaje Masivo , Factores de RiesgoRESUMEN
INTRODUCTION: In previous studies, the protective effect of colonoscopy was generally stronger for distal colorectal cancer than for proximal colorectal cancer (CRC). This study aimed to investigate whether reduction of CRC risk through colonoscopy varies according to major tumor markers and pathways of CRC. METHODS: This is a population-based case-control study from Germany, including 2,132 patients with a first diagnosis of CRC and information on major molecular tumor markers and 2,486 control participants without CRC. Detailed participant characteristics were collected by standardized questionnaires. Information on previous colonoscopy was derived from medical records. Polytomous logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between previous colonoscopy and subtypes of CRC. RESULTS: Overall, we observed strong risk reduction of CRC after colonoscopy that was weaker for microsatellite instable (MSI) than for non-MSI CRC (OR 0.70, 95% CI 0.50-0.97 vs OR 0.28, 95% CI 0.24-0.33), for CpG island methylator phenotype high CRC than for CpG island methylator phenotype low/negative CRC (OR 0.45, 95% CI 0.34-0.59 vs OR 0.29, 95% CI 0.25-0.34), for BRAF-mutated than for BRAF nonmutated CRC (OR 0.62, 95% CI 0.42-0.91 vs OR 0.30, 95% CI 0.25-0.35), for KRAS nonmutated than for KRAS-mutated CRC (OR 0.34, 95% CI 0.29-0.40 vs OR 0.26, 95% CI 0.20-0.32), and for CRC classified into the sessile serrated pathway than for CRC of the traditional pathway (OR 0.57, 95% CI 0.36-0.91 vs OR 0.30, 95% CI 0.25-0.37). After colonoscopy with the detection of adenomas or hyperplastic polyps, no risk reduction was found for sessile serrated pathway CRC, MSI, and BRAF-mutated subtypes. DISCUSSION: Our study extends the molecular understanding of existing differences in risk reduction of proximal and distal CRCs reported by previous studies and may imply important information for improving strategies for timely detection of relevant precursors.
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Adenoma/patología , Colonoscopía , Neoplasias Colorrectales/patología , Proteínas Proto-Oncogénicas B-raf , Adenoma/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Islas de CpG , Metilación de ADN , Femenino , Alemania , Humanos , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
BACKGROUND: Evidence suggests that physical activity (PA) is beneficial for reducing fatigue in colorectal cancer (CRC) survivors. However, little is known regarding long-term effects of PA on fatigue and whether pre-diagnosis PA is associated with less fatigue in the years after diagnosis. Our study aimed to investigate the association of pre- and post-diagnosis PA with long-term fatigue in CRC survivors. METHODS: This study used a German population-based cohort of 1781 individuals, diagnosed with CRC in 2003-2014, and alive at five-year follow-up (5YFU). Physical activity was assessed at diagnosis and at 5YFU. Fatigue was assessed by the Fatigue Assessment Questionnaire and the EORTC Quality of Life Questionnaire-Core 30 fatigue subscale at 5YFU. Multivariable linear regression was used to explore associations between pre- and post-diagnosis PA and fatigue at 5YFU. RESULTS: No evidence was found that pre-diagnosis PA was associated with less fatigue in long-term CRC survivors. Pre-diagnosis work-related PA and vigorous PA were even associated with higher levels of physical (Beta (ß) = 2.52, 95% confidence interval (CI) = 1.14-3.90; ß = 2.03, CI = 0.65-3.41), cognitive (ß = 0.17, CI = 0.05-0.28; ß = 0.13, CI = 0.01-0.25), and affective fatigue (ß = 0.26, CI = 0.07-0.46; ß = 0.21, CI = 0.02-0.40). In cross-sectional analyses, post-diagnosis PA was strongly associated with lower fatigue on all scales. CONCLUSIONS: In this study, pre-diagnosis PA does not appear to be associated with less fatigue among long-term CRC survivors. Our results support the importance of ongoing PA in long-term CRC survivors. Our findings might be used as a basis for further research on specific PA interventions to improve the long-term outcome of CRC survivors.
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Supervivientes de Cáncer/psicología , Neoplasias Colorrectales/rehabilitación , Ejercicio Físico , Fatiga/epidemiología , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/psicología , Estudios Transversales , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Encuestas y Cuestionarios , Tasa de SupervivenciaRESUMEN
High levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research.The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging.BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes.The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases.
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Antropometría , Índice de Masa Corporal , Peso Corporal , Femenino , Alemania , Humanos , Masculino , Circunferencia de la CinturaRESUMEN
The risk of developing colorectal cancer (CRC) is associated with a wide range of dietary and lifestyle factors. The individual contribution of single modifiable factors, such as alcohol consumption, physical activity, smoking, body mass index (BMI) or dietary components, to the development of CRC has been investigated extensively, but evidence on their combined effect at various stages of colorectal carcinogenesis is sparse. The aim of our study was to analyze the association of a healthy lifestyle pattern with prevalence of early and advanced colorectal neoplasms. A total of 13,600 participants of screening colonoscopy in Saarland/Germany (mean age 62.9 years) who were enrolled in the KolosSal study (Effektivität der Früherkennungs-Koloskopie: eine Saarland-weite Studie) from 2005 until 2013 were included in this cross-sectional analysis. Dietary and lifestyle data were collected and colonoscopy results were extracted from physicians' reports. The association of an a priori defined healthy lifestyle score-including dietary intake, alcohol consumption, physical activity, smoking and BMI-with early and advanced colorectal neoplasms was assessed by multiple logistic regression analyses with comprehensive adjustment for potential confounders. Strong inverse dose-response relationships were observed between an overall healthier lifestyle pattern and presence of advanced colorectal neoplasms, nonadvanced adenomas and hyperplastic polyps (p value <0.0001 in all cases), with adjusted odds ratios (95% CI) for the highest compared to the lowest category of the healthy lifestyle score of 0.41 (0.30-0.56), 0.42 (0.33-0.54) and 0.39 (0.29-0.54) respectively. A healthy lifestyle is strongly associated with lower risk of all stages of colorectal neoplasms.
Asunto(s)
Neoplasias Colorrectales/epidemiología , Estilo de Vida Saludable/fisiología , Tamizaje Masivo/estadística & datos numéricos , Anciano , Consumo de Bebidas Alcohólicas , Índice de Masa Corporal , Carcinogénesis/patología , Colonoscopía/estadística & datos numéricos , Estudios Transversales , Dieta , Ejercicio Físico , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Riesgo , FumarRESUMEN
OBJECTIVE: The aim of this study was to evaluate outcomes of metastases at various time intervals after colorectal cancer (CRC) diagnosis. BACKGROUND: Earlier studies have indicated a short time interval between CRC diagnosis and distant metastases to be associated with poor prognosis. The majority of studies assessed outcome from CRC diagnosis or metastasis resection rather than from metastasis diagnosis and might be subject to immortal time bias. METHODS: Patients in the population-based DACHS study were stratified: metastases at/within 1 month (immediate), 2 to 6 months (early), 7 to 12 months (intermediate), and >12 months (late) after CRC diagnosis. The primary endpoint was overall survival (OS) from metastasis diagnosis. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI). HRs were adjusted for important confounders and immortal time. RESULTS: A total of 1027 patients were included. T4 (P < 0.0001) and node-positive tumors (P < 0.0001) were more frequent in the immediate group. Lung metastases (P < 0.0001) and single-site metastases (P < 0.0001) were more prevalent in the late group. In multivariable analysis, immediate metastases were not associated with poor OS compared to metastases at later time points (late vs immediate: HR 1.21; 95% CI, 0.98-1.48). Subgroup analyses revealed poor OS of late versus immediate metastases for females (1.45; 1.08-1.96), proximal colon cancer (1.54; 1.09-2.16), and N0 (1.46; 1.00-2.12) or N1 disease (1.88; 1.17-3.05). CONCLUSIONS: Immediate or early metastases are not associated with unfavorable outcome compared to late metastases. These findings challenge the current notion of poor outcome for CRC with immediate or early metastases.
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Neoplasias Colorrectales/patología , Metástasis de la Neoplasia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND & AIMS: The combined effects of healthy lifestyle factors on colorectal cancer (CRC) risk are unclear. We aimed to develop a healthy lifestyle score, to investigate the joint effects of modifiable lifestyle factors on reduction of CRC risk and determine whether associations differ with genetic risk. METHODS: We collected data from a large population-based case-control study in Germany and used multiple logistic regression analyses to examine associations between the healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness) and CRC risk. We created a genetic risk score, based on 53 risk variants, to investigate the association of the healthy lifestyle score and risk of CRC, stratified by genetic risk. RESULTS: We included 4092 patients with CRC and 3032 individuals without CRC (controls) in our analysis. In adjusted models, compared with participants with 0 or 1 healthy lifestyle factor, participants with 2 (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.67-1.06), 3 (OR 0.62; 95% CI 0.50-0.77), 4 (OR 0.53; 95% CI 0.42-0.66), or 5 (OR 0.33; 95% CI 0.26-0.43) healthy lifestyle factors had increasingly lower risks of CRC (P trend <.0001). We found no differences among subgroups stratified by genetic risk score, history of colonoscopy, or family history of CRC. Overall, 45% of CRC cases (95% CI 34%-53%) could be attributed to nonadherence to all 5 healthy lifestyle behaviors. CONCLUSIONS: In a large population-based case-control study, we identified a combination of lifestyle factors that appears to reduce risk of CRC, regardless of the patient's genetic profile. These results reinforce the importance of primary prevention of CRC.
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Neoplasias Colorrectales/etiología , Predisposición Genética a la Enfermedad , Estilo de Vida Saludable , Tejido Adiposo , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Estudios de Casos y Controles , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/genética , Dieta , Ejercicio Físico , Femenino , Alemania , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Medición de Riesgo , Factores de Riesgo , Conducta de Reducción del Riesgo , Fumar/efectos adversosRESUMEN
BACKGROUND & AIMS: Red and processed meat intake is associated with colorectal cancer (CRC) incidence, but it is not clear if intake is associated with patient survival after diagnosis. METHODS: We pooled data from 7627 patients with stage I-IV CRC from 10 studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of intake of red and processed meat before diagnosis with overall and CRC-specific survival. RESULTS: Among 7627 patients with CRC, 2338 died, including 1576 from CRC, over a median follow-up time of 5.1 years. In multivariable-adjusted analyses, higher intake of red or processed meat was not associated with overall survival of patients with stage I-III CRC: Q4 vs Q1 red meat hazard ratio [HR], 1.08 (95% CI, 0.93-1.26) and Q4 vs Q1 processed meat HR, 1.10 (95% CI, 0.93-1.32) or with CRC-specific survival: Q4 vs Q1 red meat HR, 1.09 (95% CI, 0.89-1.33) and Q4 vs Q1 processed meat HR, 1.11 (95% CI, 0.87-1.42). Results were similar for patients with stage IV CRC. However, patients with stage I-III CRC who reported an intake of processed meat above the study-specific medians had a higher risk of death from any cause (HR, 1.12; 95% CI, 1.01-1.25) than patients who reported eating at or less than the median. CONCLUSION: In this large consortium of CRC patient cohorts, intake of red and processed meat before a diagnosis of CRC was not associated with shorter survival time after diagnosis, although a possible weak adverse association cannot be excluded. Studies that evaluate dietary data from several time points before and after cancer diagnosis are required to confirm these findings.